Muscle specific tyrosine kinase (MuSK) has been shown to be expressed in muscle fiber in which it mediates the formation of neuromuscular junctions. In this study we show that MuSK is expressed in the central nervous system (CNS), particularly in the brain and eye of rodents. In the retina MuSK was expressed in astrocytes between postnatal days 7 and 14, i.e. at the time when the eyes open. Interestingly, agrin an activator of MuSK in muscle cells was also detected in the CNS. We found that agrin was localized adjacent to MuSK-expressing astrocytes which in turn were detected close to the inner limiting membrane of the rodent retina. These findings raise an interesting possibility that, in addition to the known function in the formation of the neuromuscular junctions, MuSK may be involved in neural development. To get new insight into the functions of MuSK, a yeast-two-hybrid approach was undertaken to identify partners and/or effectors of MuSK. Two of the identified proteins interacting with the intracellular domain of MuSK were the β subunit of the protein kinase 2 (CK2β) and the carboxy-terminal part of ErbB2 interacting protein (Erbin). Further studies have shown that not only the regulatory β subunit but also the catalytic α subunit of CK2 interact with MuSK. Epitope-mapping studies define the area of Erbin comprising amino acid residues between 1175 and 1229 in the carboxy terminus of the protein is necessary for its interaction with MuSK.

1.1. Synapse The word synapse first appeared in 1897, in the seventh edition of Michael Foster’s Textbook of Physiology and describes the point of contact between two cells. Synapses are specialized structural units for cellular communication in the nervous system. The formation of synapses requires a series of steps. First, the parts of the two cells have to migrate to the place where the synapse will form. Second, these subcellular structures of the cells have to differentiate to specialized presynaptic terminals and postsynaptic membranes (Bowe and Fallon, 1995). Much of the knowledge about synapses came from the study of neuromuscular junctions.

1.2. Neuromuscular junction The neuromuscular junction (NMJ) is a synapse composed by a specialized part of a motoneuron and a muscle fiber (Hall and Sanes, 1993). The NMJ consists of the presynaptic nerve terminal, the postsynaptic muscle fiber and the presynaptic Schwann cells (PSCs, also known as “terminal” Schwann cells). Additionally between the nerve terminal and the muscle membrane, a synaptic basal lamina develops, which is composed of extracellular matrix and factors produced and secreted by both nerve and muscle (Bloch and Pumplin, 1988; Sanes and Lichtman, 1999). Neuromuscular junctions have been widely used for analyses of synaptic structure, function and development because of several advantages over the synapses from the central nervous system (Burden, 1998; Sanes and Lichtman, 1999; Wyatt and Balice-Gordon, 2003), namely size, accessibility and simplicity.

1.2.1. Development of the neuromuscular junction During development starting at about embryonic day (E) 11 in mice multinucleated skeletal muscle fibers form by fusion of precursor myoblasts. Shortly after myotubes begin to form (at E12-13 in mice), motoneurons begin to contact muscle cells (Fig.1). Motoneurons can innervate from one to over hundred muscle fibers, but each muscle fiber receives input from only one motoneuron. In the terminal branches of the motor nerve, at dense patches called active zones synaptic vesicles filled with the neurotransmitter acetylcholine (ACh) start to accumulate (Hall and Sanes, 1993). 3